MOLECULAR GENETICS AND EPIGENETICS PROGRAM (GEN) ? ABSTRACT The accumulation of heritable genetic and epigenetic changes that result in loss of function of tumor suppressors and/or inappropriate activation of proto-oncogenes is a hallmark of cancer. The goals of the Molecular Genetics and Epigenetics Program (GEN) are to understand the molecular mechanisms that underlie these defects and to uncover new targets for therapy, diagnosis, prognosis, and prevention. The Program capitalizes on the large number of outstanding investigators at UVA with research expertise in chromatin architecture, transcription, replication, mutation, repair, genomics and cellular checkpoints in cancer. The Members are organized around three main themes: (1) Chromosome function, malfunction, and cellular checkpoints; (2) Gene expression and epigenetics and cancer; (3) noncoding RNAs in cancer. The Program is led by James L. Larner, MD, PhD, chair of Radiation Oncology and an expert in DNA damage responses to radiation; and by P. Todd Stukenberg, PhD a leader in the mitosis and cell cycle fields. Through its activities, GEN provides a formal mechanism for fostering intellectual exchange and collaboration among its Members. The Program currently consists of 25 Full Members and 6 Associate Members from 11 different departments. Ten of these individuals are new to the Program or to UVA since the last renewal, and they bring considerable expertise in the bioinformatics of microarray and deep-sequencing data, large-scale genomic rearrangements (including aneuploidy), and the molecular effects of radiation and cellular responses to radiation. GEN has added a significant cohort of translational and clinical investigators whose research focus is on particular tumor types, including lung and brain tumors, or on radiation damage. Total extramural funding for the Program exceeds $8.3M, including $4.1 million from the National Cancer Institute (NCI) and over $3.1M from other NIH institutes. GEN is composed of highly productive and collaborative members with 373 total publications in the last grant period and of these 22% are intra-programmatic and 29% are inter-programmatic with other UVA Cancer Center Programs.